Faculty Bibliography

The field of additive manufacturing, 3D printing (3DP), has experienced an exponential growth over the past four decades, in part due to increased accessibility. Developments including computer-aided design and manufacturing, incorporation of more versatile materials, and improved printing techniques/equipment have stimulated growth of 3DP technologies within various industries, but most specifically the medical field. Alternatives to metals including ceramics and polymers have been garnering popularity due to their resorbable properties and physiologic similarity to extracellular matrix. 3DP has the capacity to utilize an assortment of materials and printing techniques for a multitude of indications, each with their own associated benefits. Within the field of medicine, advances in medical imaging have facilitated the integration of 3DP. In particular, the field of orthopedics has been one of the earliest medical specialties to implement 3DP. Current indications include education for patients, providers, and trainees, in addition to surgical planning. Moreover, further possibilities within orthopedic surgery continue to be explored, including the development of patient-specific implants. This review aims to highlight the use of current 3DP technology and materials by the orthopedic community, and includes comments on current trends and future direction(s) within the field.

BACKGROUND:Type 2 diabetes mellitus (T2DM) afflicts about six percent of the global population, and these patients suffer from a two-fold increased fracture risk. Thiazolidinediones (TZDs), including rosiglitazone, are commonly used medications in T2DM because they have a low incidence of monotherapy failure. It is known that rosiglitazone is associated with secondary osteoporosis, further increasing the fracture risk in an already susceptible population. However, it is not yet understood how rosiglitazone impacts endochondral bone healing after fracture. The aim of this study is to elucidate how rosiglitazone treatment impacts endochondral fracture healing, and how rosiglitazone influences the differentiation of skeletal stem and progenitor cells from the bone marrow and the periosteum. METHODS:An in-vivo mouse femur fracture model was employed to evaluate differences in fracture healing between mice treated with and without rosiglitazone chow. Fracture healing was assessed with histology and micro computed tomography (μCT). In-vitro assays utilized isolated mouse bone marrow stromal cells and periosteal cells to investigate how rosiglitazone impacts the osteogenic capability and adipogenicity of these cells. RESULTS:The in-vivo mouse femur fracture model showed that fracture callus in mice treated with rosiglitazone had significantly more adipose content than those of control mice that did not receive rosiglitazone. In addition, μCT analysis showed that rosiglitazone treated mice had significantly greater bone volume, but overall greater porosity when compared to control mice. In-vitro experimentation showed significantly less osteogenesis and more adipogenesis in bone marrow derived progenitor cells that were cultured in osteogenic media. In addition, rosiglitazone treatment alone caused significant increases in adipogenesis in both bone marrow and periosteum derived cells. CONCLUSION/CONCLUSIONS:Rosiglitazone impairs endochondral fracture healing in mice by increasing adipogenesis and decreasing osteogenesis of both bone marrow and periosteum derived skeletal progenitor cells.

PURPOSE/OBJECTIVE:To determine if the DTS decreases radiation exposure (primary outcome measure), fluoroscopy time (secondary outcome measure), and time to distal screw placement (secondary outcome measure) compared to the freehand "perfect circles" method when used for locking of cephalomedullary nails in the treatment of femur fractures METHODS: Fifty-eight patients with hip or femoral shaft fractures that were treated with a long cephalomedullary nail were enrolled in this study. Cohorts were determined based on the method of distal interlocking screw placement into either the "Perfect Circles" or "Distal Targeting" cohort. Time from cephalad screw placement to placement of final distal interlocking screw (seconds), radiation exposure (mGy), and fluoroscopy time (seconds) were compared between groups. Hospital quality measures were compared between cohorts. RESULTS:Use of the DTS resulted in 77% (4.3x) lower radiation exposure (p < 0.001), 64% (2.7x) lower fluoroscopy time (p < 0.001), and 60% (1.7x) lower intraoperative time from end of cephalad screw placement to end of distal interlocking screw placement (p < 0.001) compared to the freehand "perfect circles" method. There was no difference in 30-day or 90-day complication rates between cohorts. CONCLUSION/CONCLUSIONS:The Stryker Gamma3® Distal Targeting System is a safe, effective and efficient alternative to the freehand "perfect circles" method.

BACKGROUND:The purpose of this study is to determine if a standardized protocol for radial nerve handling during humeral shaft repair reduces the incidence of iatrogenic nerve palsy post operatively. METHODS:Seventy-three patients were identified who underwent acute or reconstructive humeral shaft repair with radial nerve exploration as part of the primary procedure for either humeral shaft fracture or nonunion. All patients exhibited intact radial nerve function pre-operatively. A retrospective chart review and analysis identified patients who developed a secondary radial nerve palsy post-operatively. In each case, the radial nerve was identified and mobilized for protection, regardless of whether the implant necessitated the extensile exposure. RESULTS:Fractures were classified according to AO/OTA guidelines and included 23 Type 12A, 11 Type 12B, and 3 Type 12C. Eight patients had periprosthetic fractures and 28 fractures could not be classified. All patients in the cohort were fixed with locking plates. Surgery was indicated for 36 patients with humeral nonunions and 37 patients with acute humeral shaft fractures. Of the 73 patients, 2 (2.7%) developed radial nerve palsy following surgery, one from the posterior approach and one from the anterolateral approach. Both patients exhibited complete recovery of radial nerve function by 6-month follow-up. No significant differences (p > 0.05) were found in any demographic or surgical details between those with and without radial nerve injury. CONCLUSIONS:Nerve exploration identification and protection leads to a low incidence of transient radial nerve palsy compared to the rate reported in the current literature (2.7% compared to 6-24%). Thus, radial nerve exploration and mobilization should be considered when approaching the humeral shaft for acute fracture and nonunion repairs. LEVEL OF EVIDENCE/METHODS:Level III.

The purpose of this study was to determine if the use of peripheral nerve blocks in the operative management of tibial plateau fractures is associated with improved outcomes when compared with the use of spinal and general anesthesia. Over a period of 16 years, 132 patients who underwent operative repair for a low-energy tibial plateau fracture and had at least 12 months of follow-up met the inclusion criteria and formed the basis of this study. Patients were grouped into cohorts based on the anesthetic method used during surgery: peripheral nerve block in combination with conscious sedation or general anesthesia (BA), general anesthesia alone (GA), or spinal anesthesia alone (SA). Outcomes were assessed at 3 months, 6 months, and 12 months. Length of stay was greatest in the GA cohort (P<.05), and more patients in the BA cohort were discharged to home (P<.05). Patients in the GA cohort had the highest pain scores at 3 months and 6 months (P<.05). Patients in both the SA and BA cohorts had better Short Musculoskeletal Function Assessment scores at 6 and 12 months when compared with the GA cohort (P<.05). Although knee range of motion did not differ among the three cohorts at 3 months, it did differ at 6 months and 12 months postoperatively, with those who had a preoperative nerve blockade (SA and BA) having the greatest knee range of motion (P<.05). Regional anesthesia was safe and was associated with lower pain scores in the early postoperative period and greater knee range of motion and functional outcome scores in the late postoperative period. [Orthopedics. 2023;46(6):358-364.].

This study compares outcomes of patients with Lisfranc injuries treated with screw only fixation constructs to those treated with dorsal plate and screw constructs. Seventy patients who underwent surgical treatment for acute Lisfranc injury without arthrodesis and minimum 6-month (mean >1-year) follow-up were identified. Demographics, surgical information, and radiographic imaging were reviewed. Cost data were compared. The primary outcome measure was the American Orthopedic Foot and Ankle Surgery (AOFAS) midfoot score. Univariate analysis through independent sample t tests, Mann-Whitney U, and chi-squared compared the populations. Twenty-three (33%) patients were treated with plate constructs and 47 (67%) with screw only fixation. The plate group was older (49 ± 18 vs 40 ± 16 years, p = .029). More screw constructs treated isolated medial column injuries compared to plate constructs (92% vs 65%, p = .006). At latest follow-up (mean 14 ± 13 months), all tarsometatarsal joints were aligned. There was no difference in AOFAS midfoot scores. Plate patients experienced longer operations (131 ± 70 vs 75 ± 31 minutes, p < .001) and tourniquet time (101 ± 41 vs 69 ± 25 minutes, p = .001). Plate constructs were more expensive than screw ($2.3X ± $2.3X vs $X ± $0.4X, p < .001) ($X is the mean cost of screws alone). Plate patients had a higher incidence of wound complications (13% vs 0%, p = .012). Treatment of Lisfranc fracture dislocation injuries with screws only demonstrated a higher value procedure as similar outcomes were found amidst lower implant costs. Screw only fixation required a shorter operative and tourniquet time with less frequent wound complications. Screw only fixations proved mechanically sound enough to achieve goals of repair without inferior outcomes.

BACKGROUND/UNASSIGNED:Locking plate technology was developed approximately 25-years-ago and has been successfully used since. Newer designs and material properties have been used to modify the original design, but these changes have yet to be correlated to improved patient outcomes. The purpose of this study was to evaluate the outcomes of first-generation locking plate (FGLP) and screw systems at our institution over an 18 year period. METHODS/UNASSIGNED:Between 2001 to 2018, 76 patients with 82 proximal tibia and distal femur fractures (both acute fracture and nonunions) who were treated with a first-generation titanium, uniaxial locking plate with unicortical screws (FGLP), also known as a LISS plate (Synthes Paoli Pa), were identified and compared to 198 patients with 203 similar fracture patterns treated with 2nd and 3rd generation locking plates, or Later Generation Locking Plates (LGLP). Inclusion criteria was a minimum of 1-year follow-up. At latest follow-up, outcomes were assessed using radiographic analysis, Short Musculoskeletal Functional Assessment (SMFA), VAS pain scores, and knee ROM. All descriptive statistics were calculated using IBM SPSS (Armonk, NY). RESULTS/UNASSIGNED:A total of 76 patients with 82 fractures had a mean 4-year follow-up available for analysis. There were 76 patients with 82 fractures fixed with a First-generation locking plate. The mean age at time of injury for all patients was 59.2 and 61.0% were female. Mean time to union for fractures about the knee fixed with FGLP was by 5.3 months for acute fractures and 6.1 months for nonunions. At final follow-up, the mean standardized SMFA for all patients was 19.9, mean knee range of motion was 1.6°-111.9°, and mean VAS pain score was 2.7. When compared to a group of similar patients with similar fractures and nonunions treated with LGLPs there were no differences in outcomes assessed. CONCLUSION/UNASSIGNED:.

Loss of bone is a common medical problem and, while it can be treated with available therapies, some of these therapies have critical side effects. We have previously demonstrated that CGS21680, a selective A_2A adenosine receptor agonist, prevents bone loss, but its on-target toxicities (hypotension, tachycardia) and frequent dosing requirements make it unusable in the clinic. We therefore generated a novel alendronate-CGS21680 conjugate (MRS7216), to target the agonist to bone where it remains for long periods thereby diminishing the frequency of administration and curtailing side effects. MRS7216 was synthesized from CGS21680 by sequential activation of the carboxylic acid moiety and reacting with an appropriate amino acid (PEG, alendronic acid) under basic conditions. MRS7216 was tested on C57BL/6J (WT) mice with established osteoporosis (OP) and WT or A2A KO mice with wear particle-induced inflammatory osteolysis (OL). Mice were treated weekly with MRS7216 (10mg/kg). Bone formation was studied after in vivo labeling with calcein/Alizarin Red, and μCT and histology analyses were performed. In addition, human primary osteoblasts and osteoclasts were cultured using bone marrow discarded after hip replacement. Receptor binding studies demonstrate that MRS7216 efficiently binds the A2A adenosine receptor. MRS7216-treated OP and OL mice had significant new bone formation and reduced bone loss compared to vehicle or alendronate-treated mice. Histological analysis showed that MRS7216 treatment significantly reduced osteoclast number and increased osteoblast number in murine models. Interestingly, cultured human osteoclast differentiation was inhibited, and osteoblast differentiation was stimulated by the compound indicating that MRS7216 conjugates represent a novel therapeutic approach to treat osteoporosis and osteolysis.

INTRODUCTION/BACKGROUND:The purpose of this study was to assess how quality and volume of common orthopaedic care varies across private, municipal, and federal healthcare delivery systems (HDSs). METHODS:Hip and knee arthroplasty, knee and shoulder arthroscopy, and hip fracture repair were audited over a two-year period. Electronic medical records were reviewed for demographics, diagnosis, lengths of stay (LoSs), surgical wait times, inpatient complication, readmission, and revision surgery rates. Multivariate regression controlled for differences in age, sex, diagnosis, and Charlson Comorbidity Index to determine how HDS correlated with surgical wait time, length of stay, complication rates, readmission, and revision surgery. RESULTS:The 5,696 included patients comprise 87.4% private, 8.6% municipal, and 4.0% federal HDSs. Compared with private HDS for arthroplasty, federal surgical wait times were 18 days shorter (95% CI = 9 to 26 days, P < 0.001); federal LoS was 4 days longer (95% CI = 3.6 to 4.3 days, P < 0.001); municipal LoS was 1 day longer (95% CI = 0.8 to 1.4, P < 0.001); municipal 1-year revision surgery odds were increased (odds ratio [OR] = 2.8, 95% CI = 1.3 to 5.4, P = 0.045); and complication odds increased for municipal (OR = 12.2, 95% CI = 5.2 to 27.4, P < 0.001) and federal (OR = 12.0, 95% CI = 4.5 to 30.8, P < 0.001) HDSs. Compared with private HDS for arthroscopy, municipal wait times were 57 days longer (95% CI = 48 to 66 days, P < 0.001) and federal wait times were 34 days longer (95% CI = 21 to 47 days, P < 0.001). Compared with private HDS for fracture repair, municipal wait times were 0.6 days longer (95% CI = 0.2 to 1.0, P = 0.02); federal LoS was 7 days longer (95% CI = 3.6 to 9.4 days, P < 0.001); and municipal LoS was 4 days longer (95% CI = 2.4 to 4.8, P < 0.001). Only private HDS fracture repair patients received bone health consultations. DISCUSSION/CONCLUSIONS:The private HDS provided care for a markedly larger volume of patients seeking orthopaedic care. In addition, private HDS patients experienced reduced surgical wait times, LoSs, and complication odds for inpatient elective cases, with better referral patterns for nonsurgical orthopaedic care after hip fractures within the private HDS. These results may guide improvements for federal and municipal HDSs.

BACKGROUND:The quality of evidence of the orthopedic literature has been often called into question. The fragility index (FI) has emerged as a means to evaluate the robustness of a significant result. Similarly, reverse fragility index (RFI) can be used for nonsignificant results to evaluate whether one can confidently conclude that there is no difference between groups. The analysis of FI and RFI in proximal humerus fracture (PHF) management is of particular interest, given ongoing controversy regarding optimal management and patient selection. The aim of this study was to report the FI, RFI and quality of the evidence in the proximal humerus fracture literature. METHODS:A systematic review was conducted based on the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines, which utilized EMBASE, MEDLINE and Cochrane Library databases. Inclusion criteria included randomized controlled clinical trials related to the management of proximal humerus fractures, published from 2000 to 2020 with dichotomous outcome measures and 1:1 allocation. The FI and RFI were calculated by successively changing one nonevent to an event for each outcome measure until the result was made nonsignificant or significant, respectively. The fragility quotient, (FQ), calculated by dividing the FI by the total sample size, was calculated as well. RESULTS:There were 25 studies that met our criteria with 48 outcome measures recorded. A total of 21 studies had at least one fragile result, with ten studies including a fragile result in the conclusion of the abstract. A total of 31 outcome measures had nonsignificant results and the median RFI was found to be 4, with 71% greater than number of patients lost to follow up. Seventeen outcomes had significant results, with a median FI of 1, with 65% greater than or equal to the number patients lost to follow up. A total of 18 of 25 studies (72%) included a power analysis. In particular, ten studies reported a statistical analysis of complication rates, 90% of which were fragile. The median FQ was found to be 0.037. CONCLUSIONS:The literature on PHF management is frequently fragile. Outcome measures are often fragile, particularly with regards to comparing complication rates and reoperation rates in treatment arms. Comparing to the studies in other subspecialties PHF RCTs are relatively more fragile and underpowered. Standardized reporting of FI, FQ and RFI can help the reader to reliably draw conclusions based on the fragility of outcome measures.